Companies with Ongoing Sickle Cell Research, Treatment Development, or Related Web Sites

The following companies are actively working on treatments related to sickle cell disease or pain management. News and links do not imply endorsement by the partners of the Sickle Cell Information Center. These sites are for information about new developing therapies.

Pharmaceutical Companies can aid the fight against pain and sickle cell complications by funding research and educational events. If you know of a web site to add to this list please send the information to aplatt@emory.edu.

For a 2002  Research Summary Article-2002 click here

Amgen Makers of   Aranesp (darbepoetin alpha) and Epogen (epoetin alfa) at http://www.amgen.com/

Amgen manufactures medications that increase bone marrow production of red blood cells when the kidney secreted hormone erythropoeitin is low. Amgen Med Info at http://www.amgenmedinfo.com/ has links to medical articles and information.

Bristol-Myers Squibb makers of Droxia® (hydroxyurea)

Bristol-Myers Squibb manufactures the medication Droxia®  or hydroxyurea  that was found to reduce pain episodes, reduce the need for blood transfusions and reduce the need for hospitalizations in sickle cell patients. For more information see the Hydrea protocol. 

For financial assistance with this medication :Instructions: to access program: 
-Call 1-800-272-4878 for form. 
-Form will be sent to physician. 
-Physician completes and signs the form, attaches a prescription, and mails to company. 
-Patient must sign the form. 
-The medication, up to six months per request, is mailed to physician. 
Comments: 
You can request up to three products per application. 
Refills are permitted as long as necessary 

Droxia® (hydroxyurea) Approved As Orphan Drug For Sickle Cell Anemia Bristol Laboratories 03/04/98

FDA Talk Paper: March 4, 1998 --- FDA has approved a new indication for the decades old cancer drug hydroxyurea (Droxia) -- as a treatment for adults who suffer from sickle cell anemia. Sickle cell anemia is a rare, inherited blood disorder that causes chronic anemia and periodic episodes of pain. About 91,000 people in the United States, mostly of African-American heritage, are affected by the disease. The following may be used to respond to questions.

Droxia has been approved -- specifically for patients over 18 who have had at least three "painful crises" in the previous year -- to reduce the frequency of these crises and the need for blood transfusions. Sickle cell anemia causes red blood cells to become brittle and sickle shaped. During a painful crisis, the sickle shaped red blood cells get stuck in narrow blood vessels, blocking
the flow of blood and oxygen to the body's tissues. These painful crises can cause pain and swelling of hands and feet, along with fever, fatigue, shortness of breath, eye problems, acute chest syndrome (a pneumonia-like condition that leads to difficulty breathing), and infections.

Although the drug is not a cure for sickle cell disease, it may help control the symptoms of the disease. Doctors establish the drug dose based on the patient's weight and blood count. While taking the drug, patients must have a blood test every two weeks to ensure that their blood count is not depressed to a level at which they might be at risk for infection or bleeding. Almost all
patients who received Droxia in the clinical trials needed to have their medication stopped for a time to allow their low blood count to return to acceptable levels.

Because sickle cell anemia affects a small population of patients, Droxia has been designated as an orphan drug. Orphan drug status guarantees the developer of an orphan product seven years of market exclusivity for the orphan drug indication following the marketing approval by the FDA, and
provides other financial incentives for drug development.

Droxia (hydroxyurea) is manufactured by Bristol Laboratories, Princeton, NJ. (Hydroxyurea is also approved by FDA under the name Hydrea for treatment of certain types of leukemia and other cancers.)

Food and Drug Administration
U.S. Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockville, MD 20857

T98-11; March 4, 1998
Consumer Inquiries: 800-532-4440

Nitric Oxide

RESULTS PROMISING FOR TREATMENT OF SICKLE CELL ANEMIA WITH NITRIC OXIDE, William A. McDade, M.D., Ph.D.

CONTACT: Denise M. Jones, Philip S. Weintraub (847) 825-5586, (619) 525-6411 (Oct. 18-22) FOR RELEASE: Monday, October 20, 1997

SAN DIEGO -- Reassessing some old theories based on new research could offer help for the thousands of sufferers with sickle cell anemia.

Nitric oxide (NO), a gas that has been used successfully to treat certain lung ailments, may have another application--the "unsickling" of sickled cells, according to the results of laboratory research conducted at the University of Chicago.

The finding, reported at the American Society of Anesthesiologists annual meeting, presents the intriguing possibility that NO may be suitable for studies in patients with sickle cell disease, anesthesiologist William A. McDade, M.D., Ph.D., said.

Sickle cell disease most frequently occurs in people of African ancestry and is caused by a flaw in the gene that makes hemoglobin, the oxygen-carrying molecule in blood. This flaw makes hemoglobin molecules stick to one another, forming rigid rods within the red blood cells. The disease gets its name from the way in which these rods distort the shape of the cells, causing them to become crescent-shaped. The rigid cells often get stuck in small blood vessels and stop the flow of blood. This condition depletes oxygen from tissues in other parts of the body causing a number of maladies, including kidney failure, diseases of the retina, strokes, pneumonia and severe pain. Ten percent of African-Americans carry the sickle cell gene, and one in 400 has the disease.

A serious, potentially life-threatening complication seen in some sickle cell disease patients is acute sickle chest syndrome. Often, this is caused by the blockage of blood vessels in the lungs or chest. NO, even in small amounts, causes smooth muscle in the blood vessel wall to relax and the entirevessel to dilate, Dr. McDade said. Anesthesiologists have administered an inhaled form of NO totreat patients with pulmonary hypertension, a condition marked by abnormally high pressure withinthe arteries and lungs. "Since nitric oxide is a powerful dilator of blood vessels and some patients with sickle cell disease suffer from episodic congestion of lung blood vessels, nitric oxide might be useful in the treatment of this problem," Dr. McDade said.

In the laboratory, researchers measured the effects of four different concentrations of NO on purified, oxygen-free samples of sickle hemoglobin. Even at the lowest concentrations, NO slowed cell sickling and even promoted the unsickling of sickled cells, Dr. McDade reported. The higher the concentration of NO, the stronger NO's favorable effect, he said.

The discovery counters research conducted more than 20 years ago that suggested NO might actually enhance the formation of sickle cells, Dr. McDade said. "These earlier findings may have led investigators to withhold NO treatment from sickle cell patients for fear of causing more cell sickling," he said.

The new findings could set the stage for clinical research, Dr. McDade said.

MEDIA NOTE: Please note, the substance used in this study is nitric oxide, not nitrous oxide, the chemical often referred to as "laughing gas," which is used as a light anesthetic in dentistry and some surgeries.

Nitric Oxide at Massachusetts General Hospital

Research News Release: 2 September 1997 Contact: Sue McGreevey, mcgreeveys@a1.mgh.harvard.edu, 617-724-2764 Massachusetts General Hospital

Nitric Oxide Gas May Treat, Prevent Sickle Cell Crisis

A study by researchers at the Massachusetts General Hospital (MGH) and other
Boston hospitals suggests that inhaled nitric oxide gas might successfully treat sickle
cell disease and its characteristic episodes of debilitating pain, called sickle cell crisis.
Described in a report in the September Journal of Clinical Investigation, the new
approach would be the first to attack directly the abnormal "sickle" hemoglobin that
causes sickle cell crisis, a condition that currently can be treated only with pain-killing drugs. If follow-up studies prove successful, patients might someday treat or prevent sickle cell crisis symptoms by self-administering nitric oxide with inhalers similar to those used by asthma patients.

"The effect of inhaled nitric oxide on sickle hemoglobin is totally separate from its
effects in the lungs, which have proven life-saving for people with several critical
illnesses," says C. Alvin Head, MD, the MGH anesthesiologist who led the study.
"This is a totally new application of this molecule, which has generated a lot of interest over the past several years."

Study co-author Kenneth Bridges, MD, director of the Joint Center for Sickle Cell
and Thalassemic Disorders at Brigham and Women's Hospital and the MGH, adds,
"This discovery gives us two things: a possible means of interrupting sickle cell crisis
once it's started -- something we don't have right now -- and a real possibility for
long-term, outpatient treatment."

In sickle cell disease, a genetic disorder, affected individuals have an abnormal form of hemoglobin, the protein in red blood cells that carries oxygen from the lungs to tissues and organs throughout the body. After this abnormal hemoglobin releases its oxygen, it clumps together into an abnormal shape, deforming the red blood cells -- normally flexible discs -- into rigid, elongated "sickle cells." These sickle cells can become stuck in tiny blood vessels, blocking blood flow to various parts of the body. The result is sickle cell crisis, excruciating pain in the affected area that can require hospitalization in the most serious cases.

The current report describes how nitric oxide causes sickle hemoglobin molecules to bind oxygen with greater affinity, which should reduce formation of the sickle cells. The result was seen both in laboratory studies and in several volunteer patients with sickle cell disease who breathed low concentrations of nitric oxide.

The common gas nitric oxide -- not to be confused with the anesthetic nitrous oxide --plays many roles in the body, including relaxation of blood vessels. Researchers at the Massachusetts General Hospital (MGH) Department of Anesthesia and Critical Care pioneered the study of nitric oxide by inhalation and have shown that it can effectively treat several life-threatening lung conditions. The gas has been successful in expanding constricted blood vessels in the lung without effecting the rest of the body's circulatory system. The effect is limited to the lungs because the gas binds with hemoglobin upon entering the bloodstream, neutralizing its vessel-expanding properties. Head explains, "Our researchers who looked at how nitric oxide binds to hemoglobin found that it had no effect on normal hemoglobin. But I started to wonder if there might be any effect on abnormal hemoglobin -- particularly in sickle cell disease."

To pursue this question, Head entered into a collaboration with several local sickle cell specialists, including Carlo Brugnara, MD, of Children's Hospital and Bridges, as well as MGH investigators specializing in nitric oxide research. They first added low concentrations of nitric oxide -- similar to those used therapeutically -- to normal red blood cells and those from sickle cell disease patients. They found that the gas, while having no effect on the normal blood cells, caused the sickle hemoglobin to hold on to oxygen more avidly than it usually would.

They then took blood samples from nine volunteer patients with sickle cell disease and three normal volunteers before and after the volunteers inhaled low levels of nitric oxide in air for 45 minutes. In eight of the nine sickle cell disease patients, breathing nitric oxide caused their red cells to give up oxygen less readily than before, while the cells from the normal patients showed no change. The increased oxygen retention by the sickle cell patients' red cells persisted for a least an hour after they breathed the nitric oxide gas.

Co-author Brugnara, director of the hematology lab in the Department of Laboratory Medicine at Children's, has conducted research into sickle cell treatment approaches designed to keep the blood cells from dehydrating. He says, "Dr. Head's very novel idea of applying this inte esting molecule to sickle cell disease may turn into one of the most significant treatment developments of this decade."

Additional co-authors of the paper include Warren M. Zapol, MD, senior author and chief of the MGH Department of Anesthesia and Critical Care; Ricardo
Martinez-Ruiz, MD, Robert Kacmarek, RRT, David Kuter, MD, and Kenneth Bloch, MD, all of the MGH.

The next step the researchers will undertake is a multi-center, randomized
double-blind study to determine whether nitric oxide inhalation acutally can decrease symptoms in patients experiencing sickle cell crisis. The earliest stages of such a study have just begin, based at the MGH.

Partners Against Pain -Purdue Pharma L.P., Norwalk, CT 06850-3590

This is a web site for the education of patients and professionals about general pain management.

Novartis - http://www.novartis.com/

Exjade(R),  (deferasirox), a Breakthrough Once-Daily Oral Iron Chelator, Receives First Approval Worldwide in the U.S. - Novartis announced today the
first approval worldwide for Exjade(R) (deferasirox) -- the first and only once-daily oral iron chelator -- by the U.S. Food and Drug Administration.
Exjade has been approved for the treatment of chronic iron overload due to blood transfusions in adults and children age two and older. Exjade is the only iron chelator administered as a drink (the tablets are dispersed in a glass of orange juice, apple juice or water), compared to the current standard of care, which often requires a subcutaneous infusion lasting eight to 12 hours per night, for five to seven nights a week for as long as
the patient continues to receive blood transfusions or has excess iron within the body. As a result, many patients may have stopped or avoided iron chelation therapy, thus risking the toxic effects of iron overload.
The approval of Exjade is expected to greatly enhance the acceptance of iron chelation therapy, especially for children, and offers a new alternative to the burdensome continuous infusion therapy. "The approval of Exjade is an advance for people like me, who have been
having blood transfusions and iron chelation for most of our lives," said Jasmine Williams, who has sickle cell disease and participated in a clinical  trial of Exjade. "With Exjade I won't have to worry about using my needle and pump. I just have to drink my medicine and not think about it again until the next day. Exjade has really made a difference in my life."
Iron overload is a potentially life-threatening and unavoidable consequence of frequent blood transfusions used to treat certain types of rare chronic blood disorders, including thalassemia and sickle cell disease as well as other rare anemias and myelodysplastic syndromes. Signs of iron overload may be detected after transfusion of about 20 units of blood. If left undiagnosed or untreated, excess iron in the body is likely to lead to damage
to the liver, heart and endocrine glands. The body has no inherent mechanism to remove excess iron, so iron chelation is used as an effective treatment for transfusion-related iron overload. http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/11-02-2005/0004207142&EDATE=

http://today.reuters.com/news/newsArticle.aspx?type=healthNews&storyID=2005-11-03T164404Z_01_FLE360214_RTRUKOC_0_US-NOVARTIS-IRON.xml&archived=False

SCDAA Shares in Excitement About Exjade, New Treatment Now Available to Treat Iron Overload http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/11-02-2005/0004207141&EDATE=

ExcessIron.com - Introduction to Iron Overload http://www.excessiron.com

IronToxicty.com  http://www.irontoxicity.com - Introduction to Iron Overload  This site explores the causes, consequences, diagnosis, and management of iron overload, a disorder which, left untreated, causes toxicities that often lead to serious health problems or premature death.

Icagen, Inc. and McNeil Consumer & Specialty Pharmaceuticals  http://www.icagen.com/

ASSERT Clinical Trial Seeks 300 People With Sickle Cell Disease
The ASSERT trial, a phase III clinical research study sponsored by Icagen, Inc. and McNeil Consumer & Specialty Pharmaceuticals, is currently underway at sites throughout the U.S. and select other countries. The study is comparing the effects of a new investigational drug (ICA-17043) to placebo with or without hydroxyurea (an oral drug used for treatment of sickle cell disease). Participants in this study must be between 16 and 65 years old and have had two or more painful crises in the last 12 months that caused them to go to the doctor or an emergency room. For more information, please call 1-877-STUDY95. http://www.clinicaltrials.gov/ct/gui/show/NCT00102791

Send mail to aplatt@emory.edu with questions or comments about this web site.
Copyright © 1997 Sickle Cell Information Center
Last modified: December 08, 2005